Digalloylresveratrol, a new phenolic acid derivative induces apoptosis and cell cycle arrest in human HT-29 colon cancer cells.
Digalloylresveratrol (DIG) is a new synthetic ester of the naturally occurring polyhydroxyphenolic substances gallic acid and resveratrol which both exert anti-cancer activity in a number of tumor cell lines. The aim of the study was to identify the biochemical effects of DIG in HT-29 human colon cancer cells. DIG induced dose-dependently apoptosis after treatment for 72 h (40 microM DIG caused apoptosis in 45% of cells). DIG led to a substantial imbalance of deoxyribonucleoside triphosphates (dNTPs), the products of the enzyme ribonucleotide reductase (RR) and directly inhibited RR as it significantly reduced the incorporation of (14)C-labeled cytidine into the DNA of tumor cells. Furthermore, DIG affected the cell division and inhibited the transition from S to G2/M phase of the cell cycle. In contrast to resveratrol or gallic acid, DIG did not inhibit cyclooxygenases I and II. When HT-29 cells were simultaneously treated with DIG and 5-FU, the standard chemotherapeutic substance for colon cancer, additive growth inhibitory effects could be observed. With respect to the various biochemical and anti-proliferative effects of DIG in HT-29 cells, we regard DIG as a potential candidate for future treatment options of colon cancer and conclude that further preclinical and in vivo studies are warranted.
Bernhaus
Astrid
A
Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, General Hospital of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
Fritzer-Szekeres
Monika
M
Grusch
Michael
M
Saiko
Philipp
P
Krupitza
Georg
G
Venkateswarlu
Somepalli
S
Trimurtulu
Golakoti
G
Jaeger
Walter
W
Szekeres
Thomas
T
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000201:enzymology / Q000473:pathology*; D005472:Fluorouracil / Q000494:pharmacology; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D019073:HT29 Cells; D006801:Humans; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D012264:Ribonucleotide Reductases / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*
D000970:Antineoplastic Agents; D013267:Stilbenes; C534866:digalloylresveratrol; D005707:Gallic Acid; D011451:Prostaglandin-Endoperoxide Synthases; D012264:Ribonucleotide Reductases; D005472:Fluorouracil